Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease

Jung Yeon Lim; Jung Eun Lee; Soon A. Park; Sang In Park; Jung Min Yon; Jeong Ah Park; Sin Soo Jeun; Seung Joon Kim; Hong Jun Lee; Sung Won Kim; Seung Ho Yang

doi:10.3390/cells11061029

Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease

Jung Yeon Lim
, Jung Eun Lee
, Soon A. Park
, Sang In Park
, Jung Min Yon
, Jeong Ah Park
, Sin Soo Jeun
, Seung Joon Kim
, Hong Jun Lee
, Sung Won Kim
, Seung Ho Yang

Catholic Univ. of Korea Coll. Med.
The Catholic University of Korea, St. Vincent's Hospital
The Catholic University of Korea Incheon St. Mary's Hospital
Chungbuk National University

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer’s disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electro-physiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ_1–42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ_1–42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ_1–42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ_1–42. Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.

Original language	English
Article number	1029
Journal	Cells
Volume	11
Issue number	6
DOIs	https://doi.org/10.3390/cells11061029
State	Published - 1 Mar 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Alzheimer’s disease
Amyloid-β peptide
HNTSCs
Human brain organoid
Osteopontin

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10.3390/cells11061029

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Lim, J. Y., Lee, J. E., Park, S. A., Park, S. I., Yon, J. M., Park, J. A., Jeun, S. S., Kim, S. J., Lee, H. J., Kim, S. W., & Yang, S. H. (2022). Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease. Cells, 11(6), Article 1029. https://doi.org/10.3390/cells11061029

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title = "Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer{\textquoteright}s Disease",

abstract = "The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer{\textquoteright}s disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electro-physiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ1{\textendash}42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ1{\textendash}42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ1{\textendash}42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ1{\textendash}42. Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.",

keywords = "Alzheimer{\textquoteright}s disease, Amyloid-β peptide, HNTSCs, Human brain organoid, Osteopontin",

author = "Lim, \{Jung Yeon\} and Lee, \{Jung Eun\} and Park, \{Soon A.\} and Park, \{Sang In\} and Yon, \{Jung Min\} and Park, \{Jeong Ah\} and Jeun, \{Sin Soo\} and Kim, \{Seung Joon\} and Lee, \{Hong Jun\} and Kim, \{Sung Won\} and Yang, \{Seung Ho\}",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = mar,

day = "1",

doi = "10.3390/cells11061029",

language = "English",

volume = "11",

journal = "Cells",

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Lim, JY, Lee, JE, Park, SA, Park, SI, Yon, JM, Park, JA, Jeun, SS, Kim, SJ, Lee, HJ, Kim, SW & Yang, SH 2022, 'Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease', Cells, vol. 11, no. 6, 1029. https://doi.org/10.3390/cells11061029

TY - JOUR

T1 - Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease

AU - Lim, Jung Yeon

AU - Lee, Jung Eun

AU - Park, Soon A.

AU - Park, Sang In

AU - Yon, Jung Min

AU - Park, Jeong Ah

AU - Jeun, Sin Soo

AU - Kim, Seung Joon

AU - Lee, Hong Jun

AU - Kim, Sung Won

AU - Yang, Seung Ho

PY - 2022/3/1

Y1 - 2022/3/1

N2 - The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer’s disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electro-physiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ1–42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ1–42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ1–42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ1–42. Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.

AB - The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer’s disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electro-physiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ1–42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ1–42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ1–42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ1–42. Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.

KW - Alzheimer’s disease

KW - Amyloid-β peptide

KW - HNTSCs

KW - Human brain organoid

KW - Osteopontin

UR - https://www.scopus.com/pages/publications/85126607492

U2 - 10.3390/cells11061029

DO - 10.3390/cells11061029

M3 - Article

C2 - 35326480

AN - SCOPUS:85126607492

SN - 2073-4409

VL - 11

JO - Cells

JF - Cells

IS - 6

M1 - 1029

ER -

Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease

Abstract

Bibliographical note

UN SDGs

Keywords

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